The metabolism of polycyclic aromatic hydrocarbons (PAH) differs in cells of different species and tissues and the significant differences between humans and experimental animals in the metabolic activation of PAH are not known. The specific aims of this proposal are to analyze and compare the activation of PAH when metabolism is mediated by intact human and hamster cells in culture and when the target cells for hydrocarbon-induced biological effects are human or hamster. The biological effects of benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene and 3-methylcholanthrene will be measured in cell-mediated mutation assays with V79 Chinese hamster cells or human diploid fibroblasts as target cells, in cell-mediated transformation assays with primary Syrian hamster embryo cells as targets, and in direct mutation assays with human epidermal cells or cells of the human hepatoma-derived cell line, Hep G2, as targets. Activation of the PAH in the cell-mediated assays will be mediated by hamster embryo, hamster epidermal, human epidermal or human Hep G2 cells and we will compare the mtabolic pathways leading to activation of the PAH under the high-cell density conditions of the mutation assays and the low-cell density conditions of the transformation assay. We will also compare the hydrocarbon-DNA adducts in the target cells of the cell-mediated mutation assays when the hydrocarbons are activated by the four types of activator cells and when the target cells are V79 Chinese hamster cells or human diploid fibroblasts. Studies such as these can help to determine if there are significant differences between humans and an experimental animal model, the hamster, in the metabolic activation of PAH and can lead to a better understanding of the steps which are essential for the conversion of PAH to biologically active derivatives.